Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.

Abstract : Substrate channeling has emerged as a common mechanism for enzymatic intermediate transfer. A conspicuous gap in knowledge concerns the use of covalent lysine imines in the transfer of carbonyl-group-containing intermediates, despite their wideuse in enzymatic catalysis. Here we show how imine chemistry operates in the transfer of covalent intermediates in pyridoxal 5'-phosphate biosynthesis by the Arabidopsis thaliana enzyme Pdx1. An initial ribose 5-phosphate lysine imine is converted to the chromophoric I320 intermediate, simultaneously bound to two lysine residues and partially vacating the active site, which creates space for glyceraldehyde 3-phosphate to bind. Crystal structures show how substrate binding, catalysis and shuttling are coupled to conformational changes around strand β6 of the Pdx1 (βα)8-barrel. The dual-specificity active site and imine relay mechanism for migration of carbonyl intermediates provide elegant solutions to the challenge of coordinating a complex sequence of reactions that follow a path of over 20 Å between substrate- and product-binding sites.
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Nature Chemical Biology, Nature Publishing Group, 2017, 13 (3), pp.290-294. 〈10.1038/nchembio.2273〉
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Soumis le : lundi 13 mars 2017 - 10:38:11
Dernière modification le : lundi 19 février 2018 - 14:34:04

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Matthew J Rodrigues, Volker Windeisen, Yang Zhang, Gabriela Guédez, Stefan Weber, et al.. Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.. Nature Chemical Biology, Nature Publishing Group, 2017, 13 (3), pp.290-294. 〈10.1038/nchembio.2273〉. 〈hal-01487798〉

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